Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000658434 | SCV000780206 | uncertain significance | not provided | 2018-05-25 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the GRIN2A gene. The L159P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The L159P variant is not observed in large population cohorts (Lek et al., 2016). The L159P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV001215292 | SCV001387028 | uncertain significance | Landau-Kleffner syndrome | 2022-07-19 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 159 of the GRIN2A protein (p.Leu159Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GRIN2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 546539). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GRIN2A protein function. |